Objectives With the advent of novel genomic and transcriptomic technologies, new urinary biomarkers have been identified and tested for bladder cancer (BCa) surveillance. To summarize the current status of urinary biomarkers for the detection of recurrence and/or progression in the follow-up of non-muscle invasive BCa patients, and to assess the value of urinary biomarkers in predicting response to intravesical Bacillus Calmette–Guerin (BCG) therapy. Methods and materials A medline/pubmed© literature search was performed. The performance of commercially available and investigational biomarkers has been reviewed. End points were cancer detection (recurrence), cancer progression, and response to BCG therapy. Results The performance requirements for biomarkers are variable according to the clinical scenario. The clinical role of urinary biomarkers in the follow-up of non-muscle invasive BCa patients remains undefined. The FDA-approved tests provide unsatisfactory sensitivity and specificity levels and their use is limited. Fluorescence in situ hybridization (FISH) has been shown to be useful in specific scenarios, mostly as a reflex test and in the setting of equivocal urinary cytology. FISH and immunocytology could conceivably be used to assess BCG response. Recently developed biomarkers have shown promising results; upcoming large trials will test their utility in specific clinical scenarios in a manner similar to a phased drug development strategy. Conclusions Current commercially available urinary biomarker-based tests are not sufficiently validated to be widely used in clinical practice. Several novel biomarkers are currently under investigation. Prospective multicenter analyses will be needed to establish their clinical relevance and value.

Objectives: To investigate prospectively the clinical utility and influence on decision‐making of Bladder EpiCheck™, a non‐invasive urine test, in the surveillance of non‐muscle‐invasive bladder cancer ( NMIBC ). Materials and Methods: Urine samples from 440 patients undergoing surveillance for NMIBC were prospectively collected at five centres and evaluated using the Bladder EpiCheck test ( NCT 02647112). A multivariable nomogram and decision‐curve analysis ( DCA ) were used to evaluate the impact of Bladder EpiCheck on decision‐making when used in routine clinical practice. The test was designed to exclude recurrent disease. Results: Data from 357 patients were available for analysis. The test had a specificity of 88% (95% confidence interval [ CI ] 84–91), a negative predictive value ( NPV ) of 94.4% (95% CI 91–97) for the detection of any cancer and an NPV of 99.3% for the detection of high‐grade cancer. In multivariable analysis, positive Bladder EpiCheck results were independently associated with any and high‐grade disease recurrence (odds ratio [ OR ] 18.1, 95% CI 8.7–40.2; P < 0.001 and OR 78.3, 95% CI 19.2–547; P < 0.001). The addition of Bladder EpiCheck to standard variables improved its predictive ability for any and high‐grade disease recurrence by a difference of 16% and 22%, respectively (area under the curve 85.9% and 96.1% for any and high‐grade cancer, respectively). DCA showed an improvement in the net benefit relative to cystoscopy over a large threshold of probability, resulting in a significant reduction in unnecessary investigations. These results were similar in subgroups assessing the impact of specific clinical features. Conclusions: Bladder EpiCheck is a robust high‐performing diagnostic test in patients with NMIBC undergoing surveillance that can potentially reduce the number of unnecessary investigations.

Purpose Use of molecular markers in urine, tissue or blood offers potential opportunities to improve understanding of bladder cancer biology which may help identify disease earlier, risk stratify patients, improve prediction of outcomes or help target therapy. Methods A review of the published literature was performed, without restriction of time. Results Despite the fast-growing literature about the topic and the approval of several urinary biomarkers for use in clinical practice, they have not reached the level of evidence for widespread utilization. Biomarkers could be used in different clinical scenarios, mainly to overcome the limitations of current diagnostic, predictive, and prognostic tools. They have been evaluated to detect bladder cancer in asymptomatic populations or those with hematuria and in surveillance of disease as adjuncts to cystoscopy. There is also a potential role as prognosticators of disease recurrence, progression and survival both in patients with non-invasive cancers and in those with advanced disease. Finally, they promise to be helpful in predicting the response to local and/or systemic chemotherapy and/or immunotherapy. Conclusions To date, due to the lack of high-quality prospective trials, the level of evidence provided by the current literature remains low and, therefore, the potential of biomarkers exceeds utilization in clinical practice.